Causal relationship between chronic hepatitis B infection and gastric ulcer: A Mendelian randomization study

Chronic hepatitis B (CHB) infection is a global health burden with various extrahepatic manifestations, but its causal relationship with gastric ulcer remains unclear. This study investigated the causal effect of CHB infection on gastric ulcer risk using Mendelian Randomization (MR). This study aimed to investigate whether CHB infection causally contributes to gastric ulcer development. We performed a 2-sample MR analysis using summary-level data from a genome-wide association study. Twenty-one single-nucleotide polymorphisms associated with CHB infection (P < 5 × 10-8, LD r² < 0.01) were selected as instrumental variables. Causal estimates were obtained using inverse-variance weighted (IVW) analysis, weighted median, simple mode, and MR-Egger regression. Sensitivity analyses (Cochran Q test, MR-PRESSO, leave-one-out, scatter plot, and funnel plot) assessed the robustness of results in both European and East Asian populations. The IVW analysis revealed that CHB infection significantly increased the risk of gastric ulcer (OR = 1.034, 95% CI: 1.016-1.053, P < .001). This association was consistently supported by the weighted median (OR = 1.035, 95% CI: 1.008-1.063, P = .010) and simple mode (OR = 1.049, 95% CI: 1.004-1.097, P = .044) method. Sensitivity analyses indicated no significant heterogeneity (Q = 12.42, P > .05), or horizontal pleiotropy (Egger intercept P = .97; MR-PRESSO global test P = .913). In the East Asian sample, IVW analysis produced similar findings (OR = 1.032, 95% CI: 1.012-1.053, P = .002). Reverse MR analysis did not support a causal effect of gastric ulcer on CHB infection. CHB infection increases the risk of gastric ulcers, emphasizing the need for considering extrahepatic manifestations in management and potential targeted interventions.